Sodium N-(hydroxymethyl)glycinate

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: 90-day oral toxicity study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to internationally accepted guidelines.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA OPP 82-1 (90-Day Oral Toxicity)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-(hydroxymethyl)glycinate

EC Number:

274-357-8

EC Name:

Sodium N-(hydroxymethyl)glycinate

Cas Number:

70161-44-3

Molecular formula:

C3H7NO3.Na

IUPAC Name:

sodium N-(hydroxymethyl)glycinate

Details on test material:

- Name of test material: Suttocide®A, the CTFA Adopted Name of Sodium Hydroxymethylglycinate- Lot/batch No.: Not specified- Purity: Not specified, but analytical studies were carried out over a twelve week period to determine whether 2%-Suttocide A solutions used in the 90 Day Oral Gavage Study at Food and Drug Research Laboratories, Inc. were stable.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:10, 40, 160 mg/kg bwBasis:actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

CAGE SIDE/CLINICAL OBSERVATIONS: Yes - Time schedule: daily two mortality checks five hours apart, once daily for external signs of toxicity- Cage side observations checked in table were included (Appendix III of the study report).BODY WEIGHT and FOOD CONSUMPTION: Yes - Time schedule for examinations: measured prior to initiation of the study (day -1), weekly thereafter, and at the time of necropsy. - Food consumption: measured weekly. - Food efficiency: Yes OPHTHALMOSCOPIC EXAMINATION: Yes - Time schedule for examinations: on all rats prior to initiation of the study and on all rats after 13 weeks of dosing. - The eyes of all rats were examined by indirect ophthalmoscopy after pupil dilation with 1% Tropica-mide. CLINICAL LABORATORY STUDIES: Yes- Blood samples for hematology and clinical chemistry determinations and urine samples for urine analysis were collected after 6 and 13 weeks of dosing from all animals.- Blood was drawn from the periorbi tal plexus (orbital sinus puncture) under light ether anesthesia. - Animals were fasted overnight prior to blood collection.* HAEMATOLOGY: Yes- Parameters: hemoglobin; hematocrit; erythrocyte count; total and differential leucocyte counts platelet count. * CLINICAL CHEMISTRY: Yes- Parameters: urea nitrogen; glutamic pyruvic transaminase (GPT) glutamic oxaloacetic transaminase (GOT) calcium; phosphorus; chloride; sodium; potassium; glucose; total bilirubin; albumin; globulin; total protein ; creatinine * URINALYSIS: Yes - Parameters: appearance; specific gravity; occult blood; protein; pH; bilirubin; urobilinogen; ketones; glucose; microscopic examination of sediment

Oestrous cyclicity (parental animals):

Not examined

Sperm parameters (parental animals):

Not examined

Litter observations:

Not applicable

Postmortem examinations (parental animals):

SACRIFICE- Male animals: All surviving animals - Maternal animals: All surviving animals GROSS NECROPSY- Gross necropsy HISTOPATHOLOGY / ORGAN WEIGHTS- Microscopic examination of paraffin embedded hema-toxylin and eosin stained tissue sections (3-5 microns) was performed on the following organs and tissues from all rats in the high dosage and control groups which were sacrificed at termination and from one rat that died during the course of the study: ovaries testes thyroid (both lobes) and parathyroidsadrenal glands liver spleen aorta stomach uterus cerebellular cortexpancreas thymus esophagus pituitary gland brain-medulla/pons heart rectum urinary bladder intestine, small (duodenum, jejunum, ileum) salivary gland (submaxillary) intestine, large (cecum, colon) sciatic nerve all gross lesionkidneys lung with mainstem bronchi lymph node (mesenteric)

Postmortem examinations (offspring):

Not applicable

Statistics:

Continuous data (body weight, food consumption, clinical parameters, absolute and relative organ weights) were analyzed using analysis of variance (Snedecor and Cochran, 1967). Differences between groups were identified using the Least Significant Difference test. Pathology inci- dence data were analyzed using Fisher's Exact test. For all statistical analyses, significance was juagea at the level of pi 0.05.

Reproductive indices:

Not applicable

Offspring viability indices:

Not applicable

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

160 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: overall effects: clinical signs; mortality; body weight; food consumption; food efficiency; ophthalmoscopic examination; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology

Remarks on result:

other: Generation: juvenile to adult in a 90-day study (migrated information)

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:

not examined

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:

not examined

Effect levels (P1)

Remarks on result:

not measured/tested

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Effect levels (F1)

Remarks on result:

not measured/tested

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Oral administration (via gavage) of Suttocide A for 90 consecutive days to Sprague-Dawley rats at levels of 10, 40 and 160 mg/kg body weight did not result in any significant toxicological or histopathological effects which were treatment related. This includes examination of both testes and uteri of exposed male and female rats, respectively.